TY - JOUR
T1 - Atomistic details of charge/space competition in the Ca2+selectivity of ryanodine receptors
AU - Liu, Chunhong
AU - Zhang, Aihua
AU - Yan, Nieng
AU - Song, Chen
N1 - Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/5/6
Y1 - 2021/5/6
N2 - Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from the sarco/endoplasmic reticulum to the cytosol and show a selectivity of Ca2+ over monovalent cations. By utilizing a recently developed multisite Ca2+ model in molecular dynamic simulations, we show that multiple cations accumulate in the upper selectivity filter of RyRs, and the small size and high valence of Ca2+ make it preferable to K+ in competition for space in this confined region of negative electrostatic potential. The presence of Ca2+ in the upper selectivity filter significantly increases the energy barrier of K+ permeation, while the presence of K+ has little impact on the Ca2+ permeation. Our results provide the atomistic details of the charge/space competition mechanism for the ion selectivity of RyRs, which ensures the robustness of their Ca2+ release function. The mechanism could be utilized in protein- and nanoengineering for valence selectivity of ion species.
AB - Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from the sarco/endoplasmic reticulum to the cytosol and show a selectivity of Ca2+ over monovalent cations. By utilizing a recently developed multisite Ca2+ model in molecular dynamic simulations, we show that multiple cations accumulate in the upper selectivity filter of RyRs, and the small size and high valence of Ca2+ make it preferable to K+ in competition for space in this confined region of negative electrostatic potential. The presence of Ca2+ in the upper selectivity filter significantly increases the energy barrier of K+ permeation, while the presence of K+ has little impact on the Ca2+ permeation. Our results provide the atomistic details of the charge/space competition mechanism for the ion selectivity of RyRs, which ensures the robustness of their Ca2+ release function. The mechanism could be utilized in protein- and nanoengineering for valence selectivity of ion species.
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U2 - 10.1021/acs.jpclett.1c00681
DO - 10.1021/acs.jpclett.1c00681
M3 - Article
C2 - 33909426
AN - SCOPUS:85106143793
SN - 1948-7185
VL - 12
SP - 4286
EP - 4291
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
IS - 17
ER -